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TW200410681A - Amino acid compound for improving central function - Google Patents

Amino acid compound for improving central function Download PDF

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Publication number
TW200410681A
TW200410681A TW092126998A TW92126998A TW200410681A TW 200410681 A TW200410681 A TW 200410681A TW 092126998 A TW092126998 A TW 092126998A TW 92126998 A TW92126998 A TW 92126998A TW 200410681 A TW200410681 A TW 200410681A
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moles
amino acid
composition
acid
serine
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TW092126998A
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Chinese (zh)
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Takeshi Abe
Hiroshi Tsuchita
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Riken
Meiji Dairies Corp
Takeshi Abe
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401Proline; Derivatives thereof, e.g. captopril
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • A61K31/405Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/4172Imidazole-alkanecarboxylic acids, e.g. histidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention relates to an amino acid compound or amino acid solution, which consists of threonine(Thr), proline(Pro), glycine(Gly), valine(Val), isoleucine(Ile), leucine(Leu), tyrosine(Tyr), phenylalanine(Phe), lysine(Lys), asparatic acid(Asp), serine(Ser), glutamine(Gln), alanine(Ala), methionine(Met), tryptophan(Trp), histiding(His) and arginine(Arg), used for central administration function. The amino acid compound has no side effect because of comprising the improvement for the central function of the nature central tiredness recovery etc.

Description

200410681 玖、發明說明: 【發明所屬之技術領域】 本發明係關於對改善中樞機能具有顯著作用的胺基酸 組成物及胺基酸組成物溶液,更詳細而言,係關於胡蜂(胡 蜂屬(V e s p a ))幼蟲分泌的唾液中所含有爲了要恢復中樞性 疲勞可給予的胺基酸組成物及胺基酸組成物溶液。 【先前技術】 本發明的作者們自以前即硏究胡蜂的幼蟲所分泌的唾 液,除了硏究出其中所含胺基酸組成物的組成,亦重複硏 φ 討其用途。 結果發現上述唾液中所含多數的胺基酸組成物中一種 命名爲VAAM的胺基酸組成物具有運動機能亢進作用(特許 第2 5 1 86 9 2號)。此運動機能亢進作用包括肌力持續、滋 養強壯、營養補給' 恢復疲勞等。 血淸素係一種生理活性胺,大量含於腦、松果體、血 小板、腸等腸親鉻細胞中,特別在腦機能的控制上扮演重 要的角色。腦內的血淸素濃度和腦的機能具有密切的關係,· 特別是高濃度會誘發疲勞感和催眠誘導等,又,因和多巴 胺等其他腦內胺的相互作用使依賴症等極端低落。對感情 和身體的控制亦具有強的作用。 人類運動時腦內的血淸素會伴隨運動時血中色胺酸的 增加而增加。推測這可能導致運動時疲勞感的增加、誘發 欲睡、倦怠感等。這類的中樞性疲勞和肌肉疲勞將阻礙運 動時性能的提昇。 -6- 200410681 【發明內容】 本發明的目的係提供可恢復中樞性疲勞、改善中樞機 能之胺基酸組成物或胺基酸溶液。 本發明係一種含有酥胺酸、脯胺酸、甘胺酸、纈胺酸、 異白胺酸、白胺酸、酪胺酸、苯丙胺酸、離胺酸、天冬胺 酸、絲胺酸、麩醯胺酸、丙胺酸、甲硫胺酸、色胺酸、組 胺酸、精胺酸組成之中樞機能改善用胺基酸組成物。又本 發明亦包括在液相中含有和這些組成相同之胺基酸組成物 溶液,較理想爲水溶液。如後述般,上述組成物或溶液中 φ 的各胺基酸有特定的理想掺合比例,此胺基酸組成物及其 溶液爲天然來源故無副作用,和其他的胺基酸組成物比較, 對降低引起中樞性疲勞的血淸素濃度的作用高,具有優越 的中樞機能改善作用。 去除此胺基酸組成物中的1或2種以上胺基酸之胺基 酸組成物不易具有上述的中樞機能改善作用,惟只去除色 胺酸的胺基酸組成物或胺基酸溶液例外,具有比上述胺基 酸組成物或溶液更優異的中樞機能改善作用。如後述般’ 41 較理想的此胺基酸組成物或溶液係含有特定的理想掺合比 例之各胺基酸。 以下詳細地說明本發明。 如上所述VAAM具有複雜的作用機制的運動機能亢進作 用’集合脂質代謝的亢進、肝機能的向上、腎機能的向上、 體溫上升等多數機能作成綜合作用之結果爲提昇運動機 能。 一 7- 200410681 從此觀點考量,可知爲要提昇運動機能亦需提 的機能。 另一方面,腦內血淸素係中樞性疲勞的原因, 動後產生的食慾不振、欲睡、倦怠感及疲勞感等係 血淸素濃度升高之故。 從血淸素量的變化探討運動時VAAM在中樞的作 知VAAM中的一種例如上述胺基酸組成物對恢復中樞 有很大的貢獻。 本發明者們發現若給予已出現中樞性疲勞且血 淸素濃度已上升的運動員上述特定組成的VAAM,可 述血淸素濃度消除疲勞感,而完成本發明。 本發明相關的第1胺基酸組成物(以下稱爲第】 含有1 7種類的胺基酸爲必須成分,以各個特定的組 含有各胺基酸較理想。亦即,酥胺酸2〜1 5莫耳、脯胺{ 莫耳、甘胺酸7〜20莫耳、纈胺酸4〜8莫耳、異白胺 莫耳、白胺酸2〜12莫耳、酪胺酸1〜9莫耳、苯丙胺酸 莫耳、離胺酸5〜1 1莫耳、天冬胺酸〇 .丨〜5莫耳、絲胺酸 莫耳、麩醯胺酸0.1〜4莫耳、丙胺酸〇.丨〜12莫耳、 酸0 . 1〜5莫耳、色胺酸〇 .丨〜5莫耳、組胺酸〇 .丨〜5 精胺酸〇 . 1〜5莫耳的比例較理想,其中亦可含有其 上述之外的胺基酸、水溶性維生素類、檸檬酸等酸 他少量的添加物。 本發明相關的第2胺基酸組成物(以下稱爲第, 以特定的組成比例含有1 6種類的胺基酸爲必須成分 昇中樞 過度運 因腦內 用,可 性疲勞 中的血 減少上 .發明) 成比例 狻4〜30 酸3〜9 :0 · 5〜5 :0.1-5 甲硫胺 莫耳及 他例如 類或其 2發明) ,係去 -8- 200410681 除第1發明的胺基酸組成物中的色胺酸之組成物’此不含 色胺酸的胺基酸組成物亦具有和第1發明相同或更佳的中 樞機能改善作用。又,各胺基酸爲L -胺基酸較理想。 第1發明及第2發明的胺基酸組成物可直接以粉末狀 攝取或溶解於水形成水溶液後攝取。攝取方法可爲經口給 藥、直腸給藥、靜脈注射、點滴等一般給藥途徑。 採取經口給藥時,除了給予組成物之外亦可和醫藥上 許可的載體、賦形劑、稀釋劑等混合,作成散劑、顆粒劑、 錠劑、膠囊劑、口含劑等。惟固體散劑和錠劑因吸收需要 φ 時間,故以經口給予組成物較理想。此時,亦可和適當的 添加材料例如氯化鈉等鹽類、pH調節劑、螯合劑作成上述 的溶液再給藥。使用注射劑時可添加適當的緩衝劑和等張 劑等,溶解於滅菌蒸留水後再使用。 攝取的時間無特別的限制,可在出現中樞疲勞等前後 的任何時間攝取’特別是在運動開始前以溶液的狀態作爲 飮用劑(例如淸涼飮料、粉末飮料、作爲醫藥品以滋養強 壯或營養補給爲目的之飮料)攝取較理想。 馨 因本發明的胺基酸組成物爲低毒性,其給予量可廣泛 地设定’可因應給予方法和使用目的而變化,通常1次 〇 . 5〜5g,較理想爲丨次丨〜2g,丨日丨〜2〇g,較理想爲給予 4〜l〇g。以溶液的形式給藥或攝取時,〇 · 5〜1〇重量%的溶液 1 A的In樂重或攝取量約爲1 〇〜丨〇 〇 〇 m 1,較理想爲i〜4重量 /°的丨谷液1次給藥或攝取1 〇 〇〜4 〇 〇 m }。 從後述的實例可淸楚得知,第丨發明及第2發明的胺 -9- 200410681 基酸組成物對降低血淸素濃度恢復中樞性疲勞具有顯著的 效果’又,因爲此胺基酸組成物係天然的胺基酸來源故毒 性低’具有極有效的中樞機能改善作用。 本發明的胺基酸組成物以上述溶液特別是水溶液的形 態使用較理想,此時第1發明及第2發明的組成物可直接 溶解於水調製成溶液,或各個胺基酸溶解於個別的水,再 組成上述比例的溶液。 【實施方式】 下述係與本發明的胺基酸組成物的中樞機能改善試驗 相關之實例及比較例,惟本發明不受限於此。 (實例1 ) VAAM的調製 混合市販的胺基酸並溶解於水中,調製包含具有規定 組成的表1中實例1欄所示的1 7種胺基酸的組成物(VAAM ) 之營養液。 運動實驗 將5週齡的ddy系雄老鼠(SPF)分成5隻爲1群,在 飼養箱中斷食12小時後將1.8% VAAM以3 7. 5//1/g-體重 的比例經口給藥,靜置3 0分鐘,對各老鼠群中的5隻進行 採血並取出腦。在剩餘的各老鼠的尾部懸掛〇 . 3 g的錘,在 3 5 °C的專用泳盆中游泳3 0分鐘後直接採血並取出腦。 取出腦及調製試驗品 取出游泳前及游泳後的腦直接測定其重量,並置於液 態氮中進行凍結。在已凍結的腦中加入9倍量的6% PCA (過 200410681 氯酸)及20 v 1的BHT (二丁基羥基甲苯),以波麗特隆· 均化機進行均化後,使用日立製的高速離心機以10, 〇〇〇 r pm 的轉速於4 °C進行離心1 0分鐘,並取2ιη 1上淸液進行凍結 乾燥。在乾燥的試驗品中加入1 0 0 // 1的0 . 1 Μ醋酸緩衝液 (ρΗ4 . 5 )使完全溶解。 血淸素的分析 採用日立製的高速層析儀(L- 6200 ),以日立製的吸 光度檢測器(L- 4000UV-VIS )測定2 80nm的吸收,使用島 津製作所製的柯羅瑪巴特紀錄器進行紀錄。使用的管柱爲 肇 ODS - S i 1 i c a ( 18c-5、 4.6x250mm),移動相貝[J 使用含 1 〇 % 甲醇和丨毫莫耳EDTA (乙二胺四乙酸)的〇 ·丨莫耳醋酸緩 衝液(P Η 4 · 5 ) ’流速爲1 . 0 m 1 / c m。測定結果如第1圖所示。 (比較例1及2) 便用表1所示的CAAM(比較例1 )或蒸留水(比較例2、 DW )取代實例1的VAAM,和實例1相同條件下對老鼠給藥, 且和實例1相同條件下測定血淸素濃度。其結果如第1圖 所示。 赢 -11- 200410681 (表1 ) 胺基酸(莫耳% ) 實例 比較例 1 1 2 VAAM CAAM DW 天冬胺酸 0.2 7.5 — 酥胺酸 7.2 2.5 — 絲胺酸 2.5 8.0 — 麩醯胺酸 3.2 19.6 一 脯胺酸 18.0 8.5 一 甘胺酸 19.1 4.5 一 丙胺酸 6.0 4.5 一 纈胺酸 5.9 5.5 — 半胱胺酸 —— 0.4 — 甲硫胺酸 0.5 2.5 一 異白胺酸 4.5 5.5 — 白胺酸 6.2 8.5 — 酪胺酸 6.0 5.0 —— 苯丙胺酸 3.8 4.0 — 離胺酸 8.6 7.0 — 色胺酸 2.2 1.0 — 組胺酸 2.6 2.5 一 精胺酸 3.5 3.0 — 200410681 有關實例1及比較例1〜2的探Ιί_ 測定結果,游泳前的血淸素濃度以實例1的VAAM給藥 群最高,比較例1的CAAM給藥群較低,比較例2的DW給 藥群最低(參考第1圖,圖表中5 - ΗΤ係指血淸素)。 游泳後的血淸素濃度以比較例1的CAAM給藥群最高, 比較例2的DW給藥群次高,實例1的VAAM給藥群最低(參 考第1圖)。 比較游泳前後的血淸素濃度,實例1的VAAM給藥群濃 度降低最多,比較例1的CAAM給藥群濃度降低較少;相反 地,比較例2的DW給藥群其血淸素濃度反而上升。 腦內的血淸素和血中的色胺酸濃度成正比,第丨圖的 圖表中游泳前的血淸素濃度最大。VAAM中的色胺酸含量爲 CAAM中色胺酸含量的2倍以上,VAAM給藥群游泳後的腦內 血淸素濃度比CAAM給藥群的濃度更低。 這些結果淸楚地顯示VAAM給藥群具有對腦特別的作 用。 上述的實施樣態係爲要以實例表示而記載,惟本發明不受 限於上述的貫施樣態’只要不脫離本發明的範圍業者們可 作各種修飾和變化。 【圖式簡單說明】 第1圖係表示在實例1、2及比較例1、2中所給予的 VAAM、VAAM-TRP、CAAM及DW和血淸素濃度的關係之圖。200410681 发明 Description of the invention: [Technical field to which the invention belongs] The present invention relates to an amino acid composition and an amino acid composition solution, which have a significant effect on improving central function. More specifically, the invention relates to wasps (Vespas ( V espa)) The saliva secreted by the larva contains an amino acid composition and an amino acid composition solution that can be administered to restore central fatigue. [Prior Art] The authors of the present invention have investigated the saliva secreted by larvae of wasps from the past. In addition to studying the composition of the amino acid composition contained therein, they have repeatedly discussed the use of φφ. As a result, it was found that one of the amino acid compositions named VAAM among most of the amino acids contained in the saliva had hyperkinetic function (Patent No. 2 5 1 86 92 2). This hyperkinetic effect includes sustained muscle strength, nourishing and strengthening, nutritional supplementation, and restoring fatigue. Heparin is a physiologically active amine, which is abundantly contained in intestinal chromaffin cells such as the brain, pineal gland, blood platelet, and intestine, and plays an important role in controlling brain function. The concentration of heparin in the brain is closely related to the function of the brain. In particular, high concentrations can induce fatigue and hypnosis. In addition, interactions with other brain amines such as dopamine cause extremely low levels of dependence. It also has a strong effect on emotional and physical control. Hemoglobin in the brain during human exercise increases with an increase in tryptophan in the blood during exercise. It is speculated that this may lead to increased fatigue during exercise, induced drowsiness, and burnout. Such central fatigue and muscle fatigue will hinder performance improvement during exercise. -6- 200410681 [Summary of the invention] The object of the present invention is to provide an amino acid composition or an amino acid solution that can restore central fatigue and improve central function. The present invention is a kind of glutamic acid, proline acid, glycine acid, valine acid, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, The composition of glutamic acid, alanine, methionine, tryptophan, histidine, and arginine can be improved by using amino acid composition. The present invention also includes a solution containing an amino acid composition having the same composition in the liquid phase, and more preferably an aqueous solution. As described below, each amino acid of φ in the above composition or solution has a specific ideal blending ratio. This amino acid composition and its solution are natural sources and have no side effects. Compared with other amino acid compositions, It has a high effect on reducing the concentration of heparin that causes central fatigue, and has a superior central function improvement effect. The amino acid composition that removes one or two or more amino acids in the amino acid composition is not easy to have the above-mentioned central function improving effect, except for the amino acid composition or the amino acid solution that only removes tryptophan. It has a better central function improving effect than the amino acid composition or solution. As will be described later, '41. This amino acid composition or solution, which is more preferable, contains each amino acid in a specific desired blending ratio. The present invention is described in detail below. As mentioned above, VAAM has a complex mechanism of hyperkinesis, which integrates the functions of hyperlipid metabolism, liver function, kidney function, and body temperature. These functions are combined to improve motor function. 1 7- 200410681 From this point of view, we know that in order to improve sports performance, we need to improve the performance. On the other hand, heparin in the brain is the cause of central fatigue. The loss of appetite, sleepiness, burnout, and fatigue caused by exercise is the cause of elevated heparin concentrations. From the change in the amount of heparin, the role of VAAM in the center during exercise is known. One of the VAAMs such as the amino acid composition described above greatly contributes to the recovery of the center. The present inventors have found that if a VAAM having the above-mentioned specific composition is given to an athlete who has experienced central fatigue and whose haematoxin concentration has risen, the haematoxin concentration can eliminate fatigue and complete the present invention. The first amino acid composition (hereinafter referred to as the "first") related to the present invention contains 17 types of amino acids as essential components, and it is desirable to contain each amino acid in each specific group. That is, glutamic acid 2 to 1 5 moles, proline {Morse, 7 ~ 20 moles of glycine, 4 ~ 8 moles of valine, isoleucine mole, leucine 2 ~ 12 moles, tyrosine 1 ~ 9 Moore, Mole phenylalanine, 5 ~ 11 Mole from lysine, 0.1 ~ 5 Mole from aspartic acid, Mole from serine, 0.1 ~ 4 Mole from glutamic acid, Alanine.丨 ~ 12 mol, acid 0.1 ~ 5 mol, tryptophan 〇. 丨 ~ 5 mol, histamine 〇. 丨 ~ 5 spermine 〇. 1 ~ 5 mol is ideal, of which A small amount of other additives such as amino acids, water-soluble vitamins, and citric acid may also be included. The second amino acid composition (hereinafter referred to as the first, containing a specific composition ratio) according to the present invention 16 types of amino acids are essential ingredients for central nervous system due to overuse of the brain, which reduces blood during fatigue. Invention) Proportionally 狻 4 ~ 30 Acids 3 ~ 9: 0 · 5 ~ 5: 0.1-5 Methionamine Mole and He (Such as the class or its 2 invention), it is -8-200410681 except for the tryptophan composition in the amino acid composition of the first invention 'This tryptophan-free amino acid composition also has the same as the first Inventing the same or better central mechanism improves the effect. Moreover, it is preferable that each amino acid is L-amino acid. The amino acid composition of the first invention and the second invention can be ingested directly as a powder or after being dissolved in water to form an aqueous solution. The ingestion method may be a general administration route such as oral administration, rectal administration, intravenous injection, and drip. In the case of oral administration, in addition to the composition, it can be mixed with pharmaceutically acceptable carriers, excipients, diluents and the like to form powders, granules, lozenges, capsules, oral preparations and the like. However, since solid powders and lozenges require φ time for absorption, it is desirable to administer the composition orally. In this case, it is also possible to administer the above solution with appropriate additives such as salts such as sodium chloride, pH adjusters, and chelating agents. When using injections, appropriate buffers and isotonic agents can be added and dissolved in sterilized distilled water before use. There is no particular limitation on the intake time, and it can be taken at any time before and after the occurrence of central fatigue, especially in the state of a solution as an elixir before exercise begins (for example, cold seasoning, powder seasoning, as a medicine to nourish and strengthen or Ideal for nutritional supplements) intake. Xin because of the amino acid composition of the present invention is low toxicity, the amount of administration can be widely set 'may vary depending on the method of administration and purpose of use, usually once 0.5 ~ 5g, more preferably 丨 times 丨 2g , 丨 day 丨 ~ 20 g, more preferably 4 ~ 10 g. When administered or ingested in the form of a solution, 0.5 to 10% by weight of the solution 1 A in In weight or ingested amount is about 10 to 丨 〇〇〇m1, more preferably i to 4 weight / °丨 Valley fluid once administered or ingested 1000 ~ 400 m}. From the examples described below, it can be clearly understood that the amine-9-200410681 base acid composition of the first and second inventions has a significant effect on reducing the concentration of heparin and recovering from central fatigue. Also, because of the amino acid composition The natural amino acid source of the system is low in toxicity and it has extremely effective central function improvement. The amino acid composition of the present invention is preferably used in the form of the above solution, especially an aqueous solution. In this case, the compositions of the first invention and the second invention can be directly dissolved in water to prepare a solution, or each amino acid is dissolved in an individual Water, and then make up the solution in the above ratio. [Embodiment] The following are examples and comparative examples related to the central function improvement test of the amino acid composition of the present invention, but the present invention is not limited thereto. (Example 1) Preparation of VAAM A commercially available amino acid was mixed and dissolved in water to prepare a nutrient solution containing a composition of 17 amino acids (VAAM) having a predetermined composition shown in the column of Example 1 in Table 1. 5 week old ddy male rats (SPF) were divided into 5 groups by exercise experiments, and 1.8% VAAM was orally administered at a ratio of 37.5 / 1/1 / g-weight after 12 hours of feeding in the feeding box. The drug was allowed to stand for 30 minutes, and blood was collected from 5 mice and the brain was removed. A 0.3 g hammer was hung from the tail of each of the remaining mice, and after swimming in a dedicated bath at 35 ° C for 30 minutes, blood was collected directly and the brain was removed. Take out the brain and prepare the test article. Take out the brain before and after swimming to measure its weight directly, and freeze it in liquid nitrogen. Nine times the amount of 6% PCA (over 200410681 chloric acid) and 20 v 1 of BHT (dibutylhydroxytoluene) were added to the frozen brain, and homogenized with a Politeron homogenizer, then Hitachi was used. The manufactured high-speed centrifuge was centrifuged at 4 ° C for 10 minutes at a speed of 10,000 r pm, and 2 μm of the supernatant was taken for freeze-drying. To the dry test article, 100 μl // 0.1 M acetic acid buffer (ρΗ4.5) was added to completely dissolve. The analysis of heparin was performed using a high-speed chromatography (L-6200) manufactured by Hitachi. The absorbance detector (L-4000UV-VIS) manufactured by Hitachi was used to measure the absorption at 2 80nm. A Cromabat recorder manufactured by Shimadzu Corporation was used. Make a record. The column used was Zhao ODS-S i 1 ica (18c-5, 4.6x250mm), mobile phase [J using a Molybdenum containing 10% methanol and 丨 mole EDTA (ethylenediaminetetraacetic acid) Ear acetate buffer (P Η 4 · 5) 'The flow rate was 1.0 m 1 / cm. The measurement results are shown in Fig. 1. (Comparative Examples 1 and 2) CAAM (Comparative Example 1) or distilled water (Comparative Examples 2, DW) shown in Table 1 were used instead of VAAM of Example 1, and administered to mice under the same conditions as in Example 1, and 1 Heparin concentration was measured under the same conditions. The results are shown in Figure 1. Win-11- 200410681 (Table 1) Amino acid (mole%) Examples Comparative Example 1 1 2 VAAM CAAM DW Aspartic acid 0.2 7.5 — Glucine 7.2 2.5 — Serine 2.5 8.0 — Branamine 3.2 19.6 Monoproline 18.0 8.5 Monoglycine 19.1 4.5 Monoalanine 6.0 4.5 Monovaline 5.9 5.5 — Cysteine — 0.4 — Methionine 0.5 2.5 Monoisoleucine 4.5 5.5 — Leucine 6.2 8.5 — Tyrosine 6.0 5.0 — Phenylalanine 3.8 4.0 — Lysine 8.6 7.0 — Tryptophan 2.2 1.0 — Histidine 2.6 2.5 Monosine 3.5 3.0 — 200410681 Related to Example 1 and Comparative Examples 1 to 2 Explore the results of the measurement. The concentration of heparin before swimming was highest in the VAAM administration group of Example 1, the CAAM administration group of Comparative Example 1 was lower, and the DW administration group of Comparative Example 2 was the lowest (refer to Figure 1, in the chart) 5-ΗΤ means heparin). The heparin concentration after swimming was the highest in the CAAM administration group in Comparative Example 1, the DW administration group in Comparative Example 2 was the highest, and the VAAM administration group in Example 1 was the lowest (see Figure 1). Comparing the concentrations of heparin before and after swimming, the concentration of the VAAM administration group in Example 1 decreased the most, and the concentration of the CAAM administration group in Comparative Example 1 decreased less; on the contrary, the concentration of heparin in the DW administration group of Comparative Example 2 rise. The heparin in the brain is directly proportional to the tryptophan concentration in the blood, and the heparin concentration before swimming is the highest in the graph in Figure 丨. The tryptophan content in VAAM is more than twice the tryptophan content in CAAM. The concentration of heparin in the brain after swimming in the VAAM administration group is lower than that in the CAAM administration group. These results clearly show that the VAAM administration group has a specific effect on the brain. The above-mentioned embodiment is described as an example, but the present invention is not limited to the above-mentioned continuous application state 'as long as the modifications and changes can be made by those skilled in the art without departing from the scope of the present invention. [Brief Description of Drawings] Fig. 1 is a graph showing the relationship between VAAM, VAAM-TRP, CAAM, DW, and heparin concentration given in Examples 1 and 2 and Comparative Examples 1 and 2.

Claims (1)

200410681 拾、申請專利範圍: 1 · 一種中樞機能改善用胺基酸組成物或胺基酸溶液,其特 徵係含有齡胺酸(Thi·)、脯胺酸(Pro)、甘胺酸(Giy)、纈 胺酸(Val)、異白胺酸(Ile)、白胺酸(Leu)、酪胺酸(Tyi)、 苯丙胺酸(Phe)、離胺酸(Lys )、天冬胺酸(Asp)、絲胺酸 (Ser)、變醯胺酸(Gin)、丙胺酸(Ala)、甲硫胺酸(Met)、 色肢酸(T r p )、組|女酸(H i s )及精胺酸(a r g )而成。 2 ·如申請專利範圍第丨項之中樞機能改善用胺基酸組成物 或胺基酸溶液’其中各胺基酸以酥胺酸2〜15莫耳、脯胺 麵 酸4〜30莫耳、甘胺酸7〜20莫耳、纈胺酸4〜8莫耳、異 白胺酸3〜9莫耳、白胺酸2〜12莫耳、酪胺酸丨〜9莫耳、 苯丙胺酸0.5〜5莫耳、離胺酸5〜11莫耳、天冬胺酸〇1〜5 莫耳、絲胺酸0.1〜5莫耳、麩醯胺酸ojm莫耳、丙胺 酸0.1〜12莫耳、甲硫胺酸0.1〜5莫耳、色胺酸ο ι〜5莫 耳、組胺酸0 · 1〜5莫耳及精胺酸〇 . 1〜5莫耳的比例組成。 3 . —種不含色胺酸之中樞機能改善用胺基酸組成物或胺基 酸溶液,其特徵係含有酥胺酸、脯胺酸、甘胺酸、纈胺着 酸、異白胺酸、白胺酸、酪胺酸、苯丙胺酸、離胺酸、 天冬胺酸、絲胺酸、麩醯胺酸、丙胺酸、甲硫胺酸、組 胺酸及精胺酸而成。 4 .如申請專利範圍第3項之不含色胺酸之中樞機能改善用 胺基酸組成物或胺基酸溶液,其中各胺基酸以酥胺酸2〜1 5 莫耳、脯胺酸4〜3 0莫耳、甘胺酸7〜2 0莫耳、纈胺酸4〜8 旲耳、異白胺酸3〜9莫耳、白胺酸2〜12旲耳、酪胺酸1〜9 -14- 200410681 莫耳、苯丙胺酸0 . 5〜5莫耳、離胺酸5〜1 1莫耳、天冬胺 酸0.1〜5莫耳、絲胺酸0.1〜5莫耳、麩醯胺酸0.1〜4莫 耳、丙胺酸0 . 1〜1 2莫耳、甲硫胺酸0 . 1〜5莫耳、組胺酸 0 . 1〜5莫耳及精胺酸0 . 1〜5莫耳的比例組成。200410681 Scope of patent application: 1 · An amino acid composition or amino acid solution for improving central function, which is characterized by aging amino acid (Thi ·), proline (Pro), and glycine (Giy) , Valine (Val), Isoleucine (Ile), Leucine (Leu), Tyrosine (Tyi), Phenylalanine (Phe), Lysine (Lys), Aspartic acid (Asp) , Serine, Serine, Gin, Ala, Met, T rp, H is and Arginine (Arg). 2 · If the cardinal function can be improved by using the amino acid composition or amino acid solution in the scope of the patent application, where each amino acid is melamine 2-15 mol, proline surface acid 4-30 mol, Glycine 7 ~ 20 moles, Valine 4 ~ 8 moles, Isoleucine 3 ~ 9 moles, Leucine 2 ~ 12 moles, Tyramic acid 丨 ~ 9 moles, Phenylalanine 0.5 ~ 5 moles, lysine 5 ~ 11 moles, aspartic acid 〇1 ~ 5 moles, serine 0.1 ~ 5 moles, glutamate ojm moles, alanine 0.1 ~ 12 moles, a Composition ratio of thiamine 0.1 ~ 5 mole, tryptophan οι ~ 5 mole, histidine 0 · 1 ~ 5 mole, and arginine 0.1 ~ 5 mole. 3. A type of amino acid composition or amino acid solution that does not contain tryptophan, which is characterized by containing glutamic acid, proline acid, glycine, valine acid, and isoleucine , Leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamine, alanine, methionine, histamine, and arginine. 4. The amino acid composition or amino acid solution that does not contain tryptophan can be used to improve the central function of the amino acid without applying tryptophan, in which each amino acid is melamine, 2-15 molar, proline 4 to 30 moles, 7 to 20 moles of glycine, 4 to 8 moles of valine, 3 to 9 moles of isoleucine, 2 to 12 moles of leucine, 1 to tyrosine 9 -14- 200410681 Mol, phenylalanine 0.5 to 5 moles, lysine 5 to 11 moles, aspartic acid 0.1 to 5 moles, serine 0.1 to 5 moles, glutamine 0.1 to 4 moles of acid, 0.1 to 12 moles of alanine, 0.1 to 5 moles of methionine, 0.1 to 5 moles of histamine and 0.1 to 5 moles of arginine Ear proportion composition. 15-15-
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